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Pigozzi, Barbara (2008) Eziopatogenesi e terapia dell'acne:
studio epidemiologico delle caratteristiche cliniche di una popolazione di pazienti affetti da acne e analisi dei polimorfismi del gene codificante per il recettore degli androgeni e del gene codificante per il citocromo P-450 1A1.
[Ph.D. thesis]

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Abstract (english)

Background:
Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles, which are located on the face, neck, chest, upper back, and upper arms. It is a pleomorphic disorders with multifactorial pathogenesis. Typically, lesions range from open and closed comedones to inflammatory papules, pustules, cysts, nodules and scarring may result.
Acne vulgaris is the most common skin disorders.
The pathogenesis of acne centers on the interaction of sebaceous hyperplasia, follicular hyperkeratinization, proliferation of Propionibacterium acnes, inflammation and immune reaction. But the aetiology is already understand and the evolution, severity and response to treatment are subject to variations. Some studies have shown the importance of genetic factors in the pathogenesis of acne, but the role of heredity on acne severity and response to treatment remains unclear.
The role of androgens is well established and their action is mediated by the androgen receptor. The amino-terminal domain of this receptor, is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic.
Recently some studies have shown an association between this polymorphism and acne and other androgens influence diseases, such as androgenetic alopecia, prostate cancer.
Other genetic studies have shown a relationship between polymorphisms in the Human cytochrome P-450 1A1 gene (CYP1A1) and acne. The cytochrome P-450 1A1 is one of the most active enzymes involved in retinoids metabolism. Retinoids are morphogenic for the sebaceous gland. In a recent study it has been signalled in acne patients a high frequency of the thymine-to-cytosine (T-to-C) transition situated at position 6235 creating an additional cleavage site for MspI.
In order to improve the treatment of patients, prognostic factors of acne severity and evolution must be studied.
Systematic assessment of the severity of acne continues to challenge the clinician. Acne is a pleomorphic disorder of variable course and anatomical distribution. For these reasons, no system has been accepted universally.

Aim:
The aim of our study was to analyze some clinic and epidemiologic features of patients affected by acne vulgaris to try to understand what role they can play in the pathogenesis of acne and if they can be prognostic factors of acne severity.
Second goal is validation of a grading system of severity, which features are accuracy and reproducibility and that can be used also by practicing clinicians.
Third purpose of this study is to test for an association between acne and acne severity, and CAG repeat length in the androgen receptor gene, and CYP1A1 polymorphism.

Patients and Methods:
A descriptive, prospective epidemiological study was conducted from January 2005 to October 2007 . It concerned patients with acne referred to Pediatrics Department and Dermatology Department for treatment of acne. We included patients with mild, moderate or severe acne. Epidemiological and clinical data, such as sex, age, age at onset, prepubertal or not, menarche age, family history of acne (father, mother, both parents, brother or others), body mass index, concomitant diseases (focusing on endocrine conditions), extension of lesion at onset, type and extension of lesions, grading of severity, therapy were collected in a data base.
The severity of acne was recorded using Global Acne Grading System (GAGS), (Doshi et al.), Leeds technique (Cunliffe score), Global Evaluation Scale (GES) at first visit and, for some patients, at 3, 6, 12 months.
We developed another grading system ("differentiated GAGS"), modifying GAGS in order to obtain a score for the face and a score for the trunk.
Epidemiologic analysis was made using t-student, Pearson e Rho di Spearman tests by software SPSS.
The polymorphisms were studied with the use of polymerase chain reaction and sequencing for the androgen receptor gene, and restriction fragment length polymorphism for CYP1A1.
Comparisons of allele and haplotype frequencies between cases and controls were analyzed by c2-tests.

Results and conclusion:
210 patients, 122 females and 88 males, aged 10-39 years, affected by mild to severe acne, were included in this study. Female showed a earlier onset compared to males. We found a role of hereditary factors. Presenting both parents affected by acne did not correlated with severity of the disease but seems with its duration.
Late onset acne appears to be different and to be caused by dissimilar pathogenetic mechanisms. It's almost exclusive of female subjects and it's not correlated with hereditary factors.
Male hormones are responsible of acne manifestation especially in particular body areas.
Female subjects usually develop acne after menarche. Patients developing acne before menarche are prone to more severe truncal involvement.
For many reasons it's important to have a separate severity index for face and trunk. We developed the "Differentiated GAGS" scoring index, that significantly correlated with the Cunliffe score index obtained with the Leeds technique. Concerning the analysis of the two genetic factors in our study population, we found a promising role of CYP450 1A1 polymorphisms. Further studies are required to clarify the role of these genetic factors in the pathogenesis of acne.


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EPrint type:Ph.D. thesis
Tutor:Basso, Giuseppe
Supervisor:Belloni Fortina, Anna
Ph.D. course:Ciclo 20 > Scuole per il 20simo ciclo > MEDICINA DELLO SVILUPPO E SCIENZE DELLA PROGRAMMAZIONE > MALATTIE RARE
Data di deposito della tesi:January 2008
Anno di Pubblicazione:January 2008
Key Words:eziopatogenesi acne, polimorfismo recettore degli androgeni, polimorfismo CYP1A1
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/35 Malattie cutanee e veneree
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Pediatria
Codice ID:535
Depositato il:02 Oct 2008
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Bibliografia

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